Virtually all patients with low Grade Non-Hodgkin's Lymphoma (LG NHL) relapse. Relapsed or refractory LG NHL is very difficult to treat, as successive treatments after relpase result in lower responses and less durable responses. Complications from relapsed or refractory disease often lead to death. Therefore, efficacious therapy in these patients would be extremely beneficial. This report describes the use of Bexxar (I-131 tositumomab), a radiolabeled CD-20 monoclonal anitbody, in these clinical situations to determine efficacy.

Materials and Methods

250 patients with LG NHL received Bexxar in 5 clinical trials and comprise the study group.

60 patients were chemotherapy refractory and 190 patients were relapsed and chemotherapy/rituximab refractory.

70% had LG NHL and 28% had transformed LG NHL

61% had bulky (> 5cm) disease and 46% had bone marrow involvement

Patients were first treated with a dosimetric dose of 450 mg of tositumomab and 35 mg of Bexxar. Three total body counts were then done and further doses were administered to achieve a total body dose of 75 cGy.

Responses were confirmed by two evaluations and all of those with long term responses (time to progression > 1 year) had confirmation by blinded oncologists and radiologists.

Median follow up was 30 months

Results

There was a 56% overall response rate, with 30% with a complete response (CR)

Median time to progression or death was 6.4 months, with 31% with time to progression or death > 1 year.

In those patients with a CR, the median duration of this response was not reached at 58.4 months

70% of those patients with a CR are alive and remain in CR up to 7.8 years

Single administration of Bexxar leads to significant efficacy and durable responses in many patients

Of those obtaining a CR, the majority of patients continue in response, out to almost 8 years.

Clinical/Scientific Implications

Low grade Non-Hodgkin's Lymphoma is seldom curable, yet seldom aggressive. The typical disease course is several incidences of relapses, with durations without disease becoming increasingly shorter. With this typical disease course, subsequent therapies are less and less effective. Bexxar combines monoclonal antibody therapy with radiation therapy to attempt to deliver tumoricidal doses directly to the tumor cells. There has been little toxicity reported with this, and often reports of efficacy. Though this study does not comment on toxicity, it does show a fair efficacy in the treatment of high-risk relapsed or refractory LG NHL. Specifically, patients with a CR (30% of the population treated) had a better overall survival. Though these numbers are definitely encouraging, unfortunately, there is never enough follow up with patients with LG NHL. Given that they can relapse even 20-25 years after treatment, it is unknown whether or not these CRs will remain durable. Additionally, though the data for those patients with a CR are encouraging, this does only represent 30% of the population, and there is no comment on the outcome of other patients. However, the fact remains that these patients were high-risk, and a durable reponse in any patients represents an improvement in therapy. There is, therefore, evidence that Bexxar will continue to play a significant role in the treatment of LG NHL.

Oncolink's ASH Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.